Advertisement

Obesities: Controversies in Diagnosis and Classification

  • Ottavio Bosello
  • Angiola Vanzo
  • Maria Pia Donataccio
  • Massimo Cuzzolaro
Chapter

Abstract

Body mass index (BMI) is still the most widely used indicator of obesity, and it is widely accepted as a strong predictor of excess weight-related mortality. However, in several clinical settings, in patients with many different diseases, an inverse association between BMI and mortality has been reported: hemodialysis, cardiovascular diseases, hypertension, stroke, diabetes, chronic obstructive pulmonary disease, surgery, etc. This counterintuitive phenomenon is now called obesity-survival paradox (OP). In recent years, two other contiguous concepts have received a great deal of attention. The expression metabolically healthy obesity (MHO) indicates a phenotype with BMI <30 but not having any metabolic syndrome component and having a homeostasis model assessment of insulin resistance, (HOMA) <2.5. On the other hand, metabolically obese normal-weight (MONW) individuals are normal-weight persons who display obesity-related phenotypic characteristics. Crucial areas of research are the interactions that link MHO, MONW, and OP with body composition, fat distribution, aging, and cardiorespiratory fitness. All these phenomena are very controversial and appear as a consequence of the frail current diagnostic definition of obesity based only on BMI. A new commonly established classification of obesities based on specific variables is needed.

References

  1. 1.
    Bosello O, Donataccio MP, Cuzzolaro M. Obesity or obesities? Controversies on the association between body mass index and premature mortality. Eat Weight Disord. 2016;21(2):165–74.  https://doi.org/10.1007/s40519-016-0278-4. Review. PMID:27043948.CrossRefPubMedGoogle Scholar
  2. 2.
    World Health Organization. Obesity and overweight. Fact sheet no 311. Updated January 2015. 2015. http://www.who.int/mediacentre/factsheets/fs311/en/. Accessed 1 Nov 2015.Google Scholar
  3. 3.
    Tomiyama AJ, Hunger JM, Nguyen-Cuu J, Wells C. Misclassification of cardio-metabolic health when using body mass index categories in NHANES 2005–2012. Int J Obes. 2016;40(5):1–4.  https://doi.org/10.1038/ijo.2016.17.CrossRefGoogle Scholar
  4. 4.
    Batsis JA, et al. Diagnostic accuracy of body mass index to identify obesity in older adults: NHANES 1999–2004. Int J Obes. 2016;40(5):761–7.  https://doi.org/10.1038/ijo.2015.243.CrossRefGoogle Scholar
  5. 5.
    Prentice AM, Jebb SA. Beyond body mass index. Obes Rev. 2001;2(3):141–7.CrossRefGoogle Scholar
  6. 6.
    Berrington de Gonzalez A, Hartge P, Cerhan JR, Flint AJ, et al. Body-mass index and mortality among 1.46 million white adults. N Engl J Med. 2010;363(23):2211–9.  https://doi.org/10.1056/NEJMoa1000367.CrossRefPubMedGoogle Scholar
  7. 7.
    Allison DB, Faith MS, Heo M, Kotler DP. Hypothesis concerning the U-shaped relation between body mass index and mortality. Am J Epidemiol. 1997;146(4):339–49.CrossRefGoogle Scholar
  8. 8.
    Whitlock G, Lewington S, Sherliker P, Clarke R, Emberson J, Halsey J, Qizilbash N, Collins R, Peto R. Body-mass index and cause-specific mortality in 900,000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009;373(9669):1083–96.  https://doi.org/10.1016/S0140-6736(09)60318-4. 1056/NEJMoa1000367.CrossRefPubMedGoogle Scholar
  9. 9.
    Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath CW Jr. Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med. 1999;341(15):1097–105.  https://doi.org/10.1056/NEJM199910073411501.CrossRefPubMedGoogle Scholar
  10. 10.
    Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA. 2013;309(1):71–82.  https://doi.org/10.1001/jama.2012.113905.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Hubert HB, Feinleib M, McNamara PM, Castelli WP. Obesity as an independent risk factor for cardiovascular disease:a 26-year follow-up of participants in the Framingham heartstudy. Circulation. 1983;67(5):968–77.CrossRefGoogle Scholar
  12. 12.
    Wilson PW, D’Agostino RB, Sullivan L, Parise H, Kannel WB. Overweight and obesity as determinants of cardiovascularrisk: the Framingham experience. Arch Intern Med. 2002;162(16):1867–72.CrossRefGoogle Scholar
  13. 13.
    Canoy D, Cairns BJ, Balkwill A, Wright FL, Green J, Reeves G, Beral V, Million Women Study Collaborators. Coronary heart disease incidence in women by waist circumference within categories ofbody mass index. Eur J Prevent Cardiol. 2013;20(5):759–62.  https://doi.org/10.1177/2047487313492631.CrossRefGoogle Scholar
  14. 14.
    Canoy D, Cairns BJ, Balkwill A, Wright FL, Green J, Reeves G, Beral V, Million Women Study Collaborators. Body mass index and incident coronary heart disease in women: a population-based prospective study. BMC Med. 2013;11:87.  https://doi.org/10.1186/1741-7015-11-87.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Capodaglio P, Faintuch J, Liuzzi A, editors. Disabling obesity. From determinants to health care models. Heidelberg: Springer; 2013.  https://doi.org/10.1007/978-3-642-35972-9.CrossRefGoogle Scholar
  16. 16.
    Bosello O, Cuzzolaro M. Obesità. Bologna: Mulino; 2013.Google Scholar
  17. 17.
    Bray G, Bouchard C, editors. Handbook of obesity. Clinicalapplications. 3rd ed. Informa Health Care: New York; 2008.Google Scholar
  18. 18.
    Bhaskaran K, Douglas I, Forbes H, Dos-Santos-Silva I, Leon DA, Smeeth L. Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5.24 million UK adults. Lancet. 2014;384(9945):755–65.  https://doi.org/10.1016/S0140-6736(14)60892-8.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37(12):1595–607.CrossRefGoogle Scholar
  20. 20.
    Reaven G. Metabolic syndrome: pathophysiology and implications for management of cardiovascular disease. Circulation. 2002;106(3):286–8.CrossRefGoogle Scholar
  21. 21.
    National Cholesterol Education Program Expert Panel on Detection Evaluation, Treatment of High Blood Cholesterol in Adults. Third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) final report. Circulation. 2002;106(25):3143–421.CrossRefGoogle Scholar
  22. 22.
    Reaven GM. Syndrome x: a short history. Ochsner J. 2001;3(3):124–5.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Reaven GM. The metabolic syndrome: requiescat in pace. Clin Chem. 2005;51(6):931–8.  https://doi.org/10.1373/clinchem.2005.048611.CrossRefPubMedGoogle Scholar
  24. 24.
    Grundy SM. Does the metabolic syndrome exist? Diabetes Care. 2006;29(7):1689–92.  https://doi.org/10.2337/dc05-2307 (discussion 1693–1686).CrossRefGoogle Scholar
  25. 25.
    Eckel RH, Alberti KG, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet. 2010;375(9710):181–3.  https://doi.org/10.1016/S0140-6736(09)61794-3.CrossRefPubMedGoogle Scholar
  26. 26.
    Reaven GM. The metabolic syndrome: time to get off the merry-go-round? J Intern Med. 2011;269(2):127–36.  https://doi.org/10.1111/j.1365-2796.2010.02325.x.CrossRefPubMedGoogle Scholar
  27. 27.
    Chaput JP, Ferraro ZM, Prud’homme D, Sharma AM. Widespread misconceptions about obesity. Can Fam Physician. 2014;60(11):973–5, 981–974.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Lavie CJ, Loberg K. The obesity paradox: when thinner means sicker and heavier means healthier. New York: Hudson Street Press; 2014.Google Scholar
  29. 29.
    Casazza K, Fontaine KR, Astrup A, Birch LL, Brown AW, Bohan Brown MM, Durant N, Dutton G, Foster EM, Heymsfield SB, McIver K, Mehta T, Menachemi N, Newby PK, Pate R, Rolls BJ, Sen B, Smith DL, Thomas DM, Allison DB. Myths, presumptions, and facts about obesity. N Engl J Med. 2013;368(5):446–54.  https://doi.org/10.1056/NEJMsa1208051.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Capodaglio P, Liuzzi A. Obesity: a disabling disease or a condition favoring disability? Eur J Phys Rehabil Med. 2013;49(3):395–8.PubMedGoogle Scholar
  31. 31.
    American Medical Association House of Delegates. Report of the council on science and public health (CSAPH). Recognition of obesity as a disease. Resolution 420 (A-13). 2013. p. 19. http://www.ama-assn.org/assets/meeting/2013a/a13-adden dum-refcomm-d.pdf. Accessed 11 Nov 2014.Google Scholar
  32. 32.
    American Association of Clinical Endocrinologists (AACE). American association of clinical endocrinologists (AACE) declares obesity a disease state. 2011. http://media.aace.com/press-release/american-association-clinical-endocrinologistsaace-declares-obesity-disease-state. Accessed 11 Nov 2014.
  33. 33.
    Bosello O, Donataccio MP. Obesity paradox. Eat Weight Disord. 2013;18(4):447–8.  https://doi.org/10.1007/s40519-013-0080-5.CrossRefPubMedGoogle Scholar
  34. 34.
    Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, Donato KA, Hu FB, Hubbard VS, Jakicic JM, Kushner RF, Loria CM, Millen BE, Nonas CA, Pi-Sunyer FX, Stevens J, Stevens VJ, Wadden TA, Wolfe BM, Yanovski SZ. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Obesity Society. Circulation. 2014;129(25 Suppl 2):S102–38.  https://doi.org/10.1161/01.cir.0000437739.71477.ee.CrossRefPubMedGoogle Scholar
  35. 35.
    Ravussin E, Ryan DH, The Obesity Society, et al. Expert Panel Report: Guidelines (2013) for the management of eat weight disord 123 overweight and obesity in adults. Obesity. 2014;22(S2):S41–S410.  https://doi.org/10.1002/oby.20660.CrossRefGoogle Scholar
  36. 36.
    Allison DB, Downey M, Atkinson RL, Billington CJ, Bray GA, Eckel RH, Finkelstein EA, Jensen MD, Tremblay A. Obesity as a disease: a white paper on evidence and arguments commissioned by the Council of the Obesity Society. Obesity. 2008;16(6):1161–77.  https://doi.org/10.1038/oby.2008.231.CrossRefPubMedGoogle Scholar
  37. 37.
    MedPage Today. AMA house votes against council, calls obesity a disease. 18 June 2013. http://www.medpagetoday.com/MeetingCoverage/AMA/39952. Accessed 1 Nov 2015.
  38. 38.
    Fleischmann E, Teal N, Dudley J, May W, Bower JD, Salahudeen K. Influence of excess weight on mortality and hospital stay in 1346 hemodialysis patients. Kidney Int. 1999;4:1560–7.  https://doi.org/10.1046/j.1523-1755.1999.00389.x.CrossRefGoogle Scholar
  39. 39.
    Kalantar-Zadeh K, Streja E, Kovesdy CP, Oreopoulos A, Noori N, Jing J, Nissenson AR, Krishnan M, Kopple JD, Mehrotra R, Anker SD. The obesity paradox and mortality associated with surrogates of body size and muscle mass in patients receiving hemodialysis. Mayo Clin Proc. 2010;85(11):991–1001.  https://doi.org/10.4065/mcp.2010.0336.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Kalantar-Zadeh K, Streja E, Molnar MZ, Lukowsky LR, Krishnan M, Kovesdy CP, Greenland S. Mortality prediction by surrogates of body composition: an examination of the obesity paradox in hemodialysis patients using composite ranking score analysis. Am J Epidemiol. 2012;175(8):793–803.  https://doi.org/10.1093/aje/kwr384.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Allison DB, Zannolli R, Faith MS, Heo M, Pietrobelli A, VanItallie TB, Pi-Sunyer FX, Heymsfield SB. Weight loss increases and fat loss decreases all-cause mortality rate: results from two independent cohort studies. Int J Obes Relat Metab Disord. 1999;23(6):603–11.CrossRefGoogle Scholar
  42. 42.
    Gruberg L, Weissman NJ, Waksman R, Fuchs S, Deible R, Pinnow EE, Ahmed LM, Kent KM, Pichard AD, Suddath WO, Satler LF, Lindsay J Jr. The impact of obesity on the short-term and long-term outcomes after percutaneous coronary intervention: the obesity paradox? J Am Coll Cardiol. 2002;39(4):578–84.CrossRefGoogle Scholar
  43. 43.
    Stokes A, Preston SH. Smoking and reverse causation create an obesity paradox in cardiovascular disease. Obesity. 2015;23(12):2485–90.  https://doi.org/10.1002/oby.21239.CrossRefPubMedGoogle Scholar
  44. 44.
    Bender R, Jockel KH, Trautner C, Spraul M, Berger M. Effect of age on excess mortality in obesity. JAMA. 1999;281(16):1498–504.CrossRefGoogle Scholar
  45. 45.
    Zamboni M, Mazzali G, Zoico E, Harris TB, Meigs JB, Di Francesco V, Fantin F, Bissoli L, Bosello O. Health consequences of obesity in the elderly: a review of four unresolved questions. Int J Obes. 2005;29(9):1011–29.  https://doi.org/10.1038/sj.ijo.0803005.CrossRefGoogle Scholar
  46. 46.
    McAuley PA, Smith NS, Emerson BT, Myers JN. The obesity paradox and cardiorespiratory fitness. J Obes. 2012;2012:951582.  https://doi.org/10.1155/2012/951582.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    McAuley PA, Kokkinos PF, Oliveira RB, Emerson BT, Myers JN. Obesity paradox and cardiorespiratory fitness in 12,417 male veterans aged 40–70 years. Mayo Clin Proc. 2010;85(2):115–21.  https://doi.org/10.4065/mcp.2009.0562.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Goel K, Thomas RJ, Squires RW, Coutinho T, Trejo-Gutierrez JF, Somers VK, Miles JM, Lopez-Jimenez F. Combined effect of cardiorespiratory fitness and adiposity on mortality in patients with coronary artery disease. Am Heart J. 2011;161(3):590–7.  https://doi.org/10.1016/j.ahj.2010.12.012.CrossRefPubMedGoogle Scholar
  49. 49.
    Kokkinos P, Faselis C, Myers J, Pittaras A, Sui X, Zhang J, McAuley P, Kokkinos JP. Cardiorespiratory fitness and the paradoxical BMI-mortality risk association inmale veterans. Mayo Clin Proc. 2014;89(6):754–62.  https://doi.org/10.1016/j.mayocp.2014.01.029.CrossRefPubMedGoogle Scholar
  50. 50.
    Sahakyan KR, Somers VK, Rodriguez-Escudero JP, et al. Normal-weight central obesity: implications for total and cardiovascular mortality. Ann Intern Med. 2015;163:827–35.  https://doi.org/10.7326/M14-252.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    McAuley PA, Beavers KM. Contribution of cardiorespiratory fitness to the obesity paradox. Prog Cardiovasc Dis. 2014;56(4):434–40.  https://doi.org/10.1016/j.pcad.2013.09.00690.CrossRefPubMedGoogle Scholar
  52. 52.
    De Schutter A, Lavie CJ, Patel DA, Milani RV. Obesity paradox and the heart: which indicator of obesity best describes this complex relationship? Curr Opin Clin Nutr Metab Care. 2013;16(5):517–24.  https://doi.org/10.1097/MCO.0b013e328363bcca.CrossRefPubMedGoogle Scholar
  53. 53.
    Ekelund U, Ward HA, Norat T, Luan J, et al. Physical activity and all-cause mortality across levels of overall and abdominal adiposity in European men and women: the European prospective investigation into cancer and nutrition study (EPIC). Am J Clin Nutr. 2015;101(3):613–21.  https://doi.org/10.3945/ajcn.114.100065.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    De Schutter A, Lavie CJ, Milani RV. The impact of obesity on risk factors and prevalence and prognosis of coronary heart disease—the obesity paradox. Prog Cardiovasc Dis. 2014;56(4):401–8.  https://doi.org/10.1016/j.pcad.2013.08.003.CrossRefPubMedGoogle Scholar
  55. 55.
    Myers J, McAuley P, Lavie CJ, Despres JP, Arena R, Kokkinos P. Physical activity and cardiorespiratory fitness as major markers of cardiovascular risk: their independent and interwoven importance to health status. Prog Cardiovasc Dis. 2015;57(4):306–14.  https://doi.org/10.1016/j.pcad.2014.09.011.CrossRefPubMedGoogle Scholar
  56. 56.
    Khan UI, Wang D, Karvonen-Gutierrez CA, Khalil N, Ylitalo KR, Santoro N. Progression from metabolically benign to at-risk obesity in perimenopausal women: a longitudinal analysis of study of women across the nation (SWAN). J Clin Endocrinol Metab. 2014;99(7):2516–25.  https://doi.org/10.1210/jc.2013-3259.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Finelli C, Tarantino G. “Obesity paradox” or “metabolically benign obesity”? Eat Weight Disord. 2013;18(3):337–8.  https://doi.org/10.1007/s40519-013-0047-6.CrossRefPubMedGoogle Scholar
  58. 58.
    Young TK, Gelskey DE. Is noncentral obesity metabolically benign? Implications for prevention from a population survey. JAMA. 1995;274(24):1939–41.CrossRefGoogle Scholar
  59. 59.
    Chang Y, Kim BK, Yun KE, Cho J, Zhang Y, Rampal S, Zhao D, Jung HS, Choi Y, Ahn J, Lima JA, Shin H, Guallar E, Ryu S. Metabolically-healthy obesity and coronary artery calcification. J Am Coll Cardiol. 2014;63(24):2679–86.  https://doi.org/10.1016/j.jacc.2014.03.042.CrossRefPubMedGoogle Scholar
  60. 60.
    Wildman RP, Muntner P, Reynolds K, McGinn AP, Rajpathak S, Wylie-Rosett J, Sowers MR. The obese without cardio-metabolic risk factor clustering and the normal-weight with cardio-metabolic risk factor clustering: prevalence and correlates of 2 phenotypes among the US population (NHANES 1999–2004). Arch Intern Med. 2008;168(15):1617–24.  https://doi.org/10.1001/archinte.168.15.1617.CrossRefPubMedGoogle Scholar
  61. 61.
    Bluher M. The distinction of metabolically ‘healthy’ from ‘unhealthy’ obese individuals. Curr Opin Lipidol. 2010;21(1):38–43.  https://doi.org/10.1097/MOL.0b013e3283346ccc.CrossRefPubMedGoogle Scholar
  62. 62.
    Boonchaya-anant P, Apovian CM. Metabolically healthy obesity—does it exist? Curr Atheroscler Rep. 2014;16(10):441.  https://doi.org/10.1007/s11883-014-0441-1.CrossRefPubMedGoogle Scholar
  63. 63.
    van Vliet-Ostaptchouk JV, Nuotio ML, Slagter SN, et al. The prevalence of metabolic syndrome and metabolically healthy obesity in Europe: a collaborative analysis of ten large cohort studies. BMC Endocr Disord. 2014;14(1):9.  https://doi.org/10.1186/1472-6823-14-9.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Gutierrez-Repiso C, et al. Variable patterns of obesity and cardio-metabolic phenotypes and their association with lifestyle factors in the Di@bet.es study. Nutr Metab Cardiovasc Dis. 2014;24:947–55.  https://doi.org/10.1016/j.numecd.2014.04.019.CrossRefPubMedGoogle Scholar
  65. 65.
    Rey-Lopez JP, de Rezende LF, Pastor-Valero M, Tess BH. The prevalence of metabolically healthy obesity: a systematic review and critical evaluation of the definitions used. Obes Rev. 2014;15(10):781–90.  https://doi.org/10.1111/obr.12198.CrossRefPubMedGoogle Scholar
  66. 66.
    Choi MK, Han YA, Roh YK. Utility of obesity indicators for metabolically healthy obesity: an observational study using the Korean National Health and Nutrition Examination Survey (2009–2010). BMC Public Health. 2014;14:1166.  https://doi.org/10.1186/1471-2458-14-1166.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Peterson MD, et al. Obesity misclassification and the metabolic syndrome in adults with functional mobility impairments: NHANES 2003–2006. Prev Med. 2014;60:71–6.  https://doi.org/10.1016/j.ypmed.2013.12.014.CrossRefPubMedGoogle Scholar
  68. 68.
    Hansen L, Netterstrøm MK, Johansen NB, Rønn PF, Vistisen D, Husemoen LLN, Jørgensen ME, Rod NH, Færch K. Metabolically healthy obesity and ischemic heart disease: a 10-year follow-up of the Inter99 study. J Clin Endocrinol Metab. 2017;102(6):1934–42.  https://doi.org/10.1210/jc.2016-3346. ISSN: 1945-7197.CrossRefPubMedGoogle Scholar
  69. 69.
    Hamer M, Stamatakis E. Metabolically healthy obesity and risk of all-cause and cardiovascular disease mortality. J Clin Endocrinol Metab. 2012;97(7):2482–8.  https://doi.org/10.1210/jc.2011-3475.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Després JP. Body fat distribution and risk of cardiovascular disease: an update. Circulation. 2012;126(10):1301–13.  https://doi.org/10.1161/CIRCULATIONAHA.111.067264.CrossRefPubMedGoogle Scholar
  71. 71.
    Arnlov J, Ingelsson E, Sundstrom J, Lind L. Impact of body mass index and the metabolic syndrome on the risk of cardiovascular disease and death in middle-aged men. Circulation. 2010;121(2):230–6.  https://doi.org/10.1161/CIRCULATIONAHA.109.887521.CrossRefPubMedGoogle Scholar
  72. 72.
    Arnlov J, Sundstrom J, Ingelsson E, Lind L. Impact of BMI and the metabolic syndrome on the risk of diabetes in middle-aged men. Diabetes Care. 2011;34(1):61–5.  https://doi.org/10.2337/dc10-0955.CrossRefPubMedGoogle Scholar
  73. 73.
    Kuk JL, Ardern CI. Are metabolically normal but obese individuals at lower risk for all-cause mortality? Diabetes Care. 2009;32(12):2297–9.  https://doi.org/10.2337/dc09-0574.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Lee SK, Kim SH, Cho GY, Baik I, Lim HE, Park CG, Lee JB, Kim YH, Lim SY, Kim H, Shin C. Obesity phenotype and incident hypertension: a prospective community-based cohort study. J Hypertens. 2013;31(1):145–51.  https://doi.org/10.1097/HJH.0b013e32835a3637.CrossRefPubMedGoogle Scholar
  75. 75.
    Lind L, Siegbahn A, Ingelsson E, Sundstrom J, Arnlov J. A detailed cardiovascular characterization of obesity without the metabolic syndrome. Arterioscler Thromb Vasc Biol. 2011;31(8):e27–34.  https://doi.org/10.1161/ATVBAHA.110.221572.CrossRefPubMedGoogle Scholar
  76. 76.
    St-Pierre AC, Cantin B, Mauriege P, Bergeron J, Dagenais GR, Despres JP, Lamarche B. Insulin resistance syndrome, body mass index and the risk of ischemic heart disease. CMAJ. 2005;172(10):1301–5.  https://doi.org/10.1503/cmaj.1040834.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Aung K, Lorenzo C, Hinojosa MA, Haffner SM. Risk of developing diabetes and cardiovascular disease in metabolically unhealthy normal-weight and metabolically healthy obese individuals. Clin Endocrinol Metab. 2014;99(2):462–8.  https://doi.org/10.1210/jc.2013-2832.CrossRefGoogle Scholar
  78. 78.
    Häring HU. Novel phenotypes of prediabetes? Diabetologia. 2016;59(9):1806–18.  https://doi.org/10.1007/s00125-016-4015-3. Review. PMID:27344314.CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Heianza Y, Arase Y, Tsuji H, Fujihara K, Saito K, Hsieh SD, Tanaka S, Kodama S, Hara S, Sone H. Metabolically healthy obesity, presence or absence of fatty liver, and risk of type 2 diabetes in Japanese individuals: toranomon hospital health management center study 20 (TOPICS 20). J Clin Endocrinol Metab. 2014;99(8):2952–60.  https://doi.org/10.1210/jc.2013-4427.CrossRefPubMedGoogle Scholar
  80. 80.
    Jung CH, Lee MJ, Hwang JY, Jang JE, Leem J, Yang DH, Kang JW, Kim EH, Park JY, Kim HK, Lee WJ. Association of metabolically healthy obesity with subclinical coronary atherosclerosis in a Korean population. Obesity. 2014;22(12):2613–20.  https://doi.org/10.1002/oby.20883.CrossRefPubMedGoogle Scholar
  81. 81.
    Chang Y, Ryu S, Choi Y, Zhang Y, Cho J, Kwon M-J, Hyun YY, Lee K-B, Kim H, Jung H-S, Yun KE, Ahn J, Rampal S, Zhao D, Suh B-S, Chung EC, Shin H, Pastor-Barriuso R, Guallar E. Metabolically healthy obesity and development of chronic kidney disease: a cohort study obesity and CKD. Ann Intern Med. 2016;164(5):305–12.  https://doi.org/10.7326/M15-1323.CrossRefPubMedGoogle Scholar
  82. 82.
    Jokela M, Hamer M, Singh-Manoux A, Batty GD, Kivimaki M. Association of metabolically healthy obesity with depressive symptoms: pooled analysis of eight studies. Mol Psychiatry. 2014;19(8):910–4.  https://doi.org/10.1038/mp.2013.162.CrossRefPubMedGoogle Scholar
  83. 83.
    Bluher M. Mechanisms in endocrinology: are metabolically healthy obese individuals really healthy? Eur J Endocrinol. 2014;171(6):R209–19.  https://doi.org/10.1530/eje-14-0540.CrossRefPubMedGoogle Scholar
  84. 84.
    Kramer CK, Zinman B, Retnakaran R. Are metabolically healthy overweight and obesity benign conditions?: a systematic review and meta-analysis. Ann Intern Med. 2013;159(11):758–69.  https://doi.org/10.7326/0003-4819-159-11-201312030-00008.CrossRefPubMedGoogle Scholar
  85. 85.
    Fan J, Song Y, Chen Y, Hui R, Zhang W. Combined effect of obesity and cardio-metabolic abnormality on the risk of cardiovascular disease: a meta-analysis of prospective cohort studies. Int J Cardiol. 2013;168(5):4761–8.  https://doi.org/10.1016/j.ijcard.2013.07.230.CrossRefPubMedGoogle Scholar
  86. 86.
    Heianza Y, Kato K, Kodama S, Suzuki A, Tanaka S, Hanyu O, Sato K, Sone H. Stability and changes in metabolically healthy overweight or obesity and risk of future diabetes: Niigata wellness study. Obesity. 2014;22(11):2420–5.  https://doi.org/10.1002/oby.20855.CrossRefPubMedGoogle Scholar
  87. 87.
    Hwang YC, Hayashi T, Fujimoto WY, Kahn SE, Leonetti DL, McNeely MJ, Boyko EJ. Visceral abdominal fat accumulation predicts the conversion of metabolically healthy obese subjects to an unhealthy phenotype. Int J Obes. 2015;39(9):1365–70.  https://doi.org/10.1038/ijo.2015.75.CrossRefGoogle Scholar
  88. 88.
    Hamer M, Bell JA, Sabia S, Batty GD, Kivimaki M. Stability of metabolically healthy obesity over 8 years: the English longitudinal study of ageing. Eur J Endocrinol. 2015;173(5):703–8.  https://doi.org/10.1530/EJE-15-0449.CrossRefPubMedGoogle Scholar
  89. 89.
    Hinnouho GM, Czernichow S, Dugravot A, Nabi H, Brunner EJ, Kivimaki M, Singh-Manoux A. Metabolically healthy obesity and the risk of cardiovascular disease and type 2 diabetes: the Whitehall II cohort study. Eur Heart J. 2015;36(9):551–9.  https://doi.org/10.1093/eurheartj/ehu123.CrossRefPubMedGoogle Scholar
  90. 90.
    Bluher S, Schwarz P. Metabolically healthy obesity from childhood to adulthood—does weight status alone matter? Metabolism. 2014;63(9):1084–92.  https://doi.org/10.1016/j.metabol.2014.06.009.CrossRefPubMedGoogle Scholar
  91. 91.
    Rey-Lopez JP, de Rezende LF, de Sa TH, Stamatakis E. Is the metabolically healthy obesity phenotype an irrelevant artifact for public health? Am J Epidemiol. 2015;182(9):737–41.  https://doi.org/10.1093/aje/kwv177.CrossRefPubMedGoogle Scholar
  92. 92.
    Bradshaw PT, Stevens J. Invited commentary: limitations and usefulness of the metabolically healthy obesity phenotype. Am J Epidemiol. 2015;182(9):742–4.  https://doi.org/10.1093/aje/kwv178.CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Muñoz-Garach A, Cornejo-Pareja I, Tinahones FJ. Does metabolically healthy obesity exist? Nutrients. 2016;8:6.  https://doi.org/10.3390/nu8060320. pii: E320.CrossRefGoogle Scholar
  94. 94.
    Dobson R, Burgess MI, Sprung VS, Irwin A, Hamer M, Jones J, Daousi C, Adams V, Kemp GJ, Shojaee-Moradie F, Umpleby M, Cuthbertson DJ. Metabolically healthy and unhealthy obesity: differential effects on myocardial function according to metabolic syndrome, rather than obesity. Int J Obes. 2016;40(1):153–61.  https://doi.org/10.1038/ijo.2015.151.CrossRefGoogle Scholar
  95. 95.
    Ortega FB, Lee DC, Katzmarzyk PT, Ruiz JR, Sui X, Church TS, Blair SN. The intriguing metabolically healthy but obese phenotype: cardiovascular prognosis and role of fitness. Eur Heart J. 2013;34(5):389–97.  https://doi.org/10.1093/eurheartj/ehs174.CrossRefPubMedGoogle Scholar
  96. 96.
    Ruderman NB, Schneider SH, Berchtold P. The “metabolically-obese,” normal-weight individual. Am J Clin Nutr. 1981;34(8):1617–21.CrossRefGoogle Scholar
  97. 97.
    Yoo HJ, Hwang SY, Hong HC, Choi HY, Seo JA, Kim SG, Kim NH, Choi DS, Baik SH, Choi KM. Association of metabolically abnormal but normal-weight (MANW) and metabolically healthy but obese (MHO) individuals with arterial stiffness and carotid atherosclerosis. Atherosclerosis. 2014;234(1):218–23.  https://doi.org/10.1016/j.atherosclerosis.2014.02.033.CrossRefPubMedGoogle Scholar
  98. 98.
    Oliveros E, Somers VK, Sochor O, Goel K, Lopez-Jimenez F. The concept of normal-weight obesity. Prog Cardiovasc Dis. 2014;56(4):426–33.  https://doi.org/10.1016/j.pcad.2013.10.003.CrossRefPubMedGoogle Scholar
  99. 99.
    Lopez-Miranda J, Perez-Martinez P. It is time to define metabolically obese but normal-weight (MONW) individuals. Clin Endocrinol. 2013;79(3):314–5.  https://doi.org/10.1111/cen.12181.CrossRefGoogle Scholar
  100. 100.
    Hamer M, et al. Waist circumference stronger predictor of death risk than BMI. Ann Intern Med. 2017;166(12):917–8.  https://doi.org/10.7326/L17-0022.CrossRefPubMedGoogle Scholar
  101. 101.
    Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C, American Heart Association, National Heart, Lung, and Blood Institute. Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation. 2004;109(3):433–8.  https://doi.org/10.1161/01.CIR.0000111245.75752.C6.CrossRefPubMedGoogle Scholar
  102. 102.
    St-Onge MP, Janssen I, Heymsfield SB. Metabolic syndrome in normal-weight Americans: new definition of the metabolically obese, normal-weight individual. Diabetes Care. 2004;27(9):2222–8.CrossRefGoogle Scholar
  103. 103.
    Romero-Corral A, Somers VK, Sierra-Johnson J, Korenfeld Y, Boarin S, Korinek J, Jensen MD, Parati G, Lopez-Jimenez F. Normal-weight obesity: a risk factor for cardio-metabolic dysregulation and cardiovascular mortality. Eur Heart J. 2010;31(6):737–46.  https://doi.org/10.1093/eurheartj/ehp487.CrossRefPubMedGoogle Scholar
  104. 104.
    Lassale C, Tzoulaki I, Moons KGM, et al. Separate and combined associations of obesity and metabolic health with coronary heart disease: a pan-European case-cohort analysis. Eur Heart J. 2018;39(5):397–406.  https://doi.org/10.1093/eurheartj/ehx448.CrossRefPubMedPubMedCentralGoogle Scholar
  105. 105.
    Carnethon MR, De Chavez PJ, Biggs ML, Lewis CE, Pankow JS, Bertoni AG, Golden SH, Liu K, Mukamal KJ, Campbell-Jenkins B, Dyer AR. Association of weight status with mortality in adults with incident diabetes. JAMA. 2012;308(6):581–90.  https://doi.org/10.1001/jama.2012.9282.CrossRefPubMedPubMedCentralGoogle Scholar
  106. 106.
    Logue J, Wild S, Sattar N. BMI and mortality among adults with incident type 2 diabetes. N Engl J Med. 2014;370(14):1362.  https://doi.org/10.1056/NEJMc1401876#SA3.CrossRefPubMedGoogle Scholar
  107. 107.
    Badoud F, Perreault M, Zulyniak MA, Mutch DM. Molecular insights into the role of white adipose tissue in metabolically unhealthy normal-weight and metabolically healthy obese individuals. FASEB J. 2015;29(3):748–58.  https://doi.org/10.1096/fj.14-263913.CrossRefPubMedGoogle Scholar
  108. 108.
    Khan UI, Ogorodnikova AD, Xu L, Wang D, Wassertheil-Smoller S, Ho GY, Sowers MF, Rajpathak SN, Allison MA, Mackey RH, Vitolins MZ, Manson JE, Wildman RP. The adipokine profile of metabolically benign obese and at-risk normal-weight postmenopausal women: the women’s health initiative observational study. Obesity. 2014;22(3):786–94.  https://doi.org/10.1002/oby.20139.CrossRefPubMedGoogle Scholar
  109. 109.
    Stefan N, Häring HU, Schulze MB. Metabolically healthy obesity: the low-hanging fruit in obesity treatment? Lancet Diabetes Endocrinol. 2018;6(3):249–58.  https://doi.org/10.1016/S2213-8587(17)30292-9. pii: S2213-8587(17)30292-9.CrossRefPubMedGoogle Scholar
  110. 110.
    Banack HR, Kaufman JS. The obesity paradox: understanding the effect of obesity on mortality among individuals with cardiovascular disease. Prev Med. 2014;62:96–102.  https://doi.org/10.1016/j.ypmed.2014.02.003.CrossRefPubMedGoogle Scholar
  111. 111.
    Banack HR, Kaufman JS. From bad to worse: collider stratification amplifies confounding bias in the “obesity paradox”. Eur J Epidemiol. 2015;30(10):1111–4.  https://doi.org/10.1007/s10654-015-0069-7.CrossRefPubMedGoogle Scholar
  112. 112.
    Greenberg JA. The obesity paradox in the US population. Am J Clin Nutr. 2013;97(6):1195–200.  https://doi.org/10.3945/ajcn.112.045815.CrossRefPubMedGoogle Scholar
  113. 113.
    Sperrin M, Candlish J, Badrick E, Renehan AG, Buchan I. Collider bias is only a partial explanation for the obesity paradox. Epidemiology. 2016;27(4):525–30. http://journals.lww.com/epidem/Pages/comingsoon.aspx.CrossRefGoogle Scholar
  114. 114.
    Ahima RS, Lazar MA. The health risk of obesity—better metrics imperative. Science. 2013;341(6148):856–8.  https://doi.org/10.1126/science.1241244.CrossRefPubMedGoogle Scholar
  115. 115.
    Blundell JE, Dulloo AG, Salvador J, Fruhbeck G, EASO SAB Working Group on BMI. Beyond BMI—phenotyping the obesities. Obes Facts. 2014;7(5):322–8.  https://doi.org/10.1159/000368783.CrossRefPubMedPubMedCentralGoogle Scholar
  116. 116.
    Gray SL, Vidal-Puig AJ. Adipose tissue expandability in the maintenance of metabolic homeostasis. Nutr Rev. 2007;65(6 Pt 2):S7–12.CrossRefGoogle Scholar
  117. 117.
    Moreno-Indias I, Tinahones FJ. Impaired adipose tissue expandability and lipogenic capacities as ones of the main causes of metabolic disorders. J Diabetes Res. 2015;2015:970375.  https://doi.org/10.1155/2015/970375.CrossRefPubMedPubMedCentralGoogle Scholar
  118. 118.
    Bays H. Adiposopathy, “sick fat,” ockham’s razor, and resolution of the obesity paradox. Curr Atheroscler Rep. 2014;16:409.  https://doi.org/10.1007/s11883-014-0409.CrossRefPubMedPubMedCentralGoogle Scholar
  119. 119.
    Bays H. Adiposopathy. Is “sick fat” a cardiovascular disease. J Am Coll Cardiol. 2011;57:2461–73.  https://doi.org/10.1016/j.jacc.2011.02.038.CrossRefPubMedGoogle Scholar
  120. 120.
    Muller MJ. From BMI to functional body composition. Eur J Clin Nutr. 2013;67(11):1119–21.  https://doi.org/10.1038/ejcn.2013.174.CrossRefPubMedGoogle Scholar
  121. 121.
    Muller MJ, Lagerpusch M, Enderle J, Schautz B, Heller M, Bosy-Westphal A. Beyond the body mass index: tracking body composition in the pathogenesis of obesity and the metabolic syndrome. Obes Rev. 2012;13(Suppl 2):6–13.  https://doi.org/10.1111/j.1467-789X.2012.01033.x.CrossRefPubMedGoogle Scholar
  122. 122.
    Wellen KE, Hotamisligil GS. Obesity-induced inflammatory changes in adipose tissue. J Clin Invest. 2003;112:1785–8.  https://doi.org/10.1172/JCI200320514.CrossRefPubMedPubMedCentralGoogle Scholar
  123. 123.
    Fogelholm M. Physical activity, fitness and fatness: relations to mortality, morbidity and disease risk factors. A systematic review. Obes Rev. 2010;11(3):202–21.  https://doi.org/10.1111/j.467-789X.2009.00653.x.CrossRefPubMedGoogle Scholar
  124. 124.
    Global BMI Mortality Collaboration, Di Angelantonio E, et al. Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. Lancet. 2016;388(10046):776–86.  https://doi.org/10.1016/S0140-6736(16)30175-1. Epub 2016 Jul 13.CrossRefPubMedGoogle Scholar
  125. 125.
    Chang Y, Ryu S, Suh BS, Yun KE, Kim CW, Cho SI. Impact of BMI on the incidence of metabolic abnormalities in metabolically healthy men. Int J Obes Lond. 2012;36(9):1187–94.  https://doi.org/10.1038/ijo.2011.247.CrossRefPubMedGoogle Scholar
  126. 126.
    Willett W, et al. Guidelines for healthy weight. N Engl J Med. 1999;341:427–34.  https://doi.org/10.1056/NEJM199908053410607.CrossRefPubMedGoogle Scholar
  127. 127.
    Bangalore S, et al. Body-weight fluctuations and outcomes in coronary disease. N Engl J Med. 2017;376:1332–40.  https://doi.org/10.1056/NEJMoa1606148.CrossRefPubMedGoogle Scholar
  128. 128.
    Roberson LL, Aneni EC, Maziak W, Agatston A, Feldman T, Rouseff M, Tran T, Blaha MJ, Santos RD, Sposito A, Al-Mallah MH, Blankstein R, Budoff MJ, Nasir K. Beyond BMI: the “metabolically healthy obese” phenotype and its association with clinical/subclinical cardiovascular disease and all-cause mortality—a systematic review. BMC Public Health. 2014;14:14.  https://doi.org/10.1186/1471-2458-14-14.CrossRefPubMedPubMedCentralGoogle Scholar
  129. 129.
    Phillips CM. Metabolically healthy obesity: definitions, determinants and clinical implications. Rev Endocr Metab Disord. 2013;14(3):219–27.  https://doi.org/10.1007/s11154-013-9252-x.CrossRefPubMedGoogle Scholar
  130. 130.
    Phillips CM, Dillon C, Harrington JM, McCarthy VJ, Kearney PM, Fitzgerald AP, Perry IJ. Defining metabolically healthy obesity: role of dietary and lifestyle factors. PLoS One. 2013;8(10):e76188.  https://doi.org/10.1371/journal.pone.0076188.CrossRefPubMedPubMedCentralGoogle Scholar
  131. 131.
    Volkow ND, Wang GJ, Tomasi D, Baler RD. Obesity and addiction: neurobiological overlaps. Obes Rev. 2013;14(1):2–18.  https://doi.org/10.1111/j.1467-789X.2012.01031.x.CrossRefPubMedGoogle Scholar
  132. 132.
    Smith DG, Robbins TW. The neurobiological underpinnings of obesity and binge eating: a rationale for adopting the food addiction model. Biol Psychiatry. 2013;73(9):804–10.  https://doi.org/10.1016/j.biopsych.2012.08.026.CrossRefPubMedGoogle Scholar
  133. 133.
    Harvard Health Publications. Obesity paradox? Just a myth. Harv Heart Lett. 2014;24(8):8.Google Scholar
  134. 134.
    Hill JO, Wyatt HR. The myth of healthy obesity. Ann Intern Med. 2013;159(11):789–90.  https://doi.org/10.7326/0003-4819-159-11-201312030-00016.CrossRefPubMedGoogle Scholar
  135. 135.
    Sharma AM, Kushner RF. A proposed clinical staging system for obesity. Int J Obes. 2009;33(3):289–95.CrossRefGoogle Scholar
  136. 136.
    Kuk JL, Ardern CI, Church TS, Sharma AM, Padwal R, Sui X, Blair SN. Edmonton obesity staging system: association with weight history and mortality risk. Appl Physiol Nutr Metab. 2011;36(4):570–6.  https://doi.org/10.1139/h11-058.CrossRefPubMedGoogle Scholar
  137. 137.
    Canning KL, Brown RE, Wharton S, Sharma AM, Kuk JL. Edmonton obesity staging system prevalence and association with weight loss in a publicly funded referral-based obesity clinic. J Obes. 2015;2015:619734.  https://doi.org/10.1155/2015/619734.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Ottavio Bosello
    • 1
  • Angiola Vanzo
    • 2
  • Maria Pia Donataccio
    • 1
  • Massimo Cuzzolaro
    • 3
  1. 1.Department of MedicineUniversity of VeronaVeronaItaly
  2. 2.Department of Food Hygiene and NutritionULSS 8 BericaVicenzaItaly
  3. 3.Formerly Medical Pathophysiology Department, Eating Disorders and Obesity UnitSapienza University of RomeRomeItaly

Personalised recommendations